Table 1.

Benefits of combined antiangiogenic and active immune therapies

Antiangiogenic strategyImmunotherapyTumor modelResults
Anti-mouse VEGF mAbPeptide-pulsed DCsSarcomaThe number and function of DCs.
Tumor growth delay (24).
Anti-VEGFR2 mAbGM-CSF secreting, neu-specific whole tumor cell vaccineNeu-expressing breast carcinomaInfiltration of CD8+ T cell.
Tumor regression (in FVB mice, but not neu-N/FVB mice; ref. 27).
Anti-mouse VEGF mAbPVIMelanomaImmune cell infiltration.
Tumor growth delay (26).
Rgs5 knockoutACTInsulinoma, fibrosarcomaImmune cell infiltration.
Survival (7).
Low-dose anti-VEGFR2 mAbMitomycin C–treated whole breast tumor cell vaccineBreast carcinomaInfiltration of CD8+ and CD4+ T cells.
MDSCs and Tregs.
Survival (8).
Adenoviral delivery of sVEGFR1/R2GM-CSF–secreting whole tumor cell vaccineMelanoma, colon carcinomaThe number of activated CD4+ and CD8+ T cells.
Decrease Treg.
Survival (32).
SU6668Recombinant murine B7.2-IgG fusion protein and irradiated whole tumor cell vaccineBreast carcinomaInfiltration of CD8+ T cells.
Tumor growth delay (33).
SunitinibIntratumoral IL-12 gene delivery by adenoviral vector plus 4-1BB activationColon carcinomaInfiltration of CD8+ and CD4+ T cells.
MDSC and Tregs.
Survival (34).
SunitinibPatients with renal cell carcinomaMDSC and Tregs.
Type 1 T-cell activity (35).
Low-dose TNF-αAdoptive T-cell transferInsulinomaInfiltration of CD8+ T cell.
Survival (30).

NOTE: SU6668 is an inhibitor of tyrosine kinase activity of the angiogenic receptors VEGFR2, PDGFRβ, and FGFR1. Sunitinib is an inhibitor of tyrosine kinase activity of VEGFR2, PDGFR, Flt3, and c-kit.

Abbreviations: ACT, adoptive cell transfer; GM-CSF, granulocyte-macrophage colony-stimulating factor; mAb, monoclonal antibody; VEGFR2, VEGF receptor 2; PVI, the administration of anti-GP100 transgenic pmel-1 T cells plus gp100 vaccine plus IL-2 injection after 500cGy lymphodepleting whole body irradiation.